Week 96 resistance analysis in participants receiving bictegravir/lenacapavir in the phase 2 ARTISTRY-1 study.

BackgroundARTISTRY-1 is an ongoing Phase 2/3 study evaluating the safety and efficacy of once-daily oral bictegravir (BIC) + lenacapavir (LEN) in virologically suppressed (VS; HIV-1 RNA <50 copies/mL) participants on complex antiretroviral (ARV) regimens. Here, we report Week 96 extension-phase data after transition to BIC/LEN single-tablet regimen (STR).MethodsParticipants without known integrase strand-transfer inhibitor (INSTI) resistance were randomized (2:2:1) to BIC + LEN (75mg + 25mg or 75mg + 50mg) or stable background regimen, respectively. At the end of randomized treatment (mean of 69 weeks from baseline), participants could choose to enter the extension period and receive BIC/LEN 75/50 mg STR. Baseline resistance-associated mutations (RAMs) were evaluated from cumulative historical genotypic reports (HGRs) and Day 1 proviral DNA genotyping using a composite baseline sequence. Resistance testing was performed for confirmed virologic rebound.ResultsOf 128 randomized/dosed participants, 119 entered the extension period and received BIC/LEN STR for a median time of 96 weeks (range 11-109) from end of randomization to cutoff date. Baseline RAMs were common (nucleoside reverse transcriptase inhibitor 82%, non-nucleoside reverse transcriptase inhibitor 66%, protease inhibitor 47%; INSTI RAMs 9% (proviral DNA)). Two participants met criteria for resistance testing before resuppressing, with no treatment-emergent capsid or integrase RAMs. All 119 participants were suppressed at last observed visit.ConclusionsDurable viral suppression was maintained for up to 96 weeks in the Phase 2 extension, with all participants in the extension phase maintaining virologic suppression and no treatment-emergent resistance to study drugs, supporting long-term virologic durability of BIC/LEN STR in VS individuals on complex ART.